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Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation

Author

Listed:
  • Joschka Heil

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Victor Olsavszky

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Katrin Busch

    (German Cancer Research Center (DKFZ))

  • Kay Klapproth

    (German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Carolina Torre

    (Heidelberg University)

  • Carsten Sticht

    (Heidelberg University)

  • Kajetan Sandorski

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Johannes Hoffmann

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Hiltrud Schönhaber

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Johanna Zierow

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology)

  • Manuel Winkler

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Christian David Schmid

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Theresa Staniczek

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Deborah E. Daniels

    (University of Bristol)

  • Jan Frayne

    (University of Bristol)

  • Georgia Metzgeroth

    (Heidelberg University)

  • Daniel Nowak

    (Heidelberg University)

  • Sven Schneider

    (Heidelberg University)

  • Michael Neumaier

    (Heidelberg University)

  • Vanessa Weyer

    (Heidelberg University
    Heidelberg University)

  • Christoph Groden

    (Heidelberg University)

  • Hermann-Josef Gröne

    (Philipps-University)

  • Karsten Richter

    (German Cancer Research Center (DKFZ))

  • Carolin Mogler

    (Technical University Munich)

  • Makoto Mark Taketo

    (Kyoto University)

  • Kai Schledzewski

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Cyrill Géraud

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University
    University Medical Center and Medical Faculty Mannheim, Heidelberg University)

  • Sergij Goerdt

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

  • Philipp-Sebastian Koch

    (University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology
    Heidelberg University)

Abstract

Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis. Mice with stabilized β-catenin in BM-SEC (Ctnnb1OE-SEC) generated by using a BM-SEC-restricted Cre mouse line (Stab2-iCreF3) develop fatal anemia. While activation of Wnt-signaling in BM-SEC causes an increase in erythroblast subsets (PII–PIV), mature erythroid cells (PV) are reduced indicating impairment of terminal erythroid differentiation/reticulocyte maturation. Transplantation of Ctnnb1OE-SEC hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1OE-SEC BM-SEC reveal aberrant sinusoidal differentiation with altered EC gene expression and perisinusoidal ECM deposition and angiocrine dysregulation with de novo endothelial expression of FGF23 and DKK2, elevated in anemia and involved in vascular stabilization, respectively. Our study demonstrates that BM-SEC play an important role in the bone marrow microenvironment in health and disease.

Suggested Citation

  • Joschka Heil & Victor Olsavszky & Katrin Busch & Kay Klapproth & Carolina Torre & Carsten Sticht & Kajetan Sandorski & Johannes Hoffmann & Hiltrud Schönhaber & Johanna Zierow & Manuel Winkler & Christ, 2021. "Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27161-3
    DOI: 10.1038/s41467-021-27161-3
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